Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05018546 |
| Other study ID # |
21/(6-11)/E2/077/078 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 24, 2020 |
| Est. completion date |
December 24, 2021 |
Study information
| Verified date |
May 2022 |
| Source |
Tribhuvan University Teaching Hospital, Institute Of Medicine. |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Urolithiasis is one of the most prevalent urological diseases affecting general population
across the world. The available treatment modalities for renal stones are Shock wave
lithotripsy (SWL), Percutaneous Nephrolithotomy (PNL), and Retrograde Intrarenal Surgery
(RIRS). Irrigation for RIRS is the critical component for the success of procedure. To avoid
detrimental effects of high pressure, intra-renal pressure (IRP) has to be lower. Different
studies have shown that high irrigation pressure raises intra-renal pressure leading to
pyelo-venous and pyelo-lymphatic reflux which can lead to sepsis and septic shock.
Comparative study of different irrigation pressure during RIRS is lacking.
This is randomized controlled trial conducted in Department of Urology and Renal Transplant
Surgery for duration of one year. Objective of the study is to compare safety and efficacy of
gravity irrigation versus pressure irrigation. Patients with symptomatic kidney stones: non
lower pole stones <2cm, lower pole stones <1cm and lower pole stones 1-2 cm in whom PCNL is
contraindicated will be enrolled in study with informed consent. Retrograde intrarenal
surgery will be performed as standard procedure and Ho:YAG laser will be used to fragment
stones.
Stone free rate at postoperative day 1 and after 1 month will be monitored through X-ray KUB.
Maximum irrigation pressure, duration of surgery, stone size, density, location,
intraoperative and postoperative complications as classified by Clavien-Dindo will be noted
for all patients. Data will be appropriately analyzed and statistical tests applied as
necessary.
Description:
Introduction Urolithiasis is one of the most prevalent urological diseases affecting general
population across the world. The worldwide prevalence ranges from 7%- 13% in North America,
5%-9% in Europe, and 1%-5% in Asia.1 West Asia, Southeast Asia, South Asia as well as several
developed countries, including South Korea and Japan, have been categorized into stone
forming belt countries with prevalence ranging from 5% to 19.1%. Increasing incidence of
stone disease is linked with modern life style, food habits, climate as well as increasing
use of imaging (computed tomography or ultrasonography)2,3,4 Renal stones constitute about
80% of total urolithiasis. Shock wave lithotripsy(SWL), Percutaneous Nephrolithotomy(PNL),
and Retrograde Intrarenal Surgery (RIRS) are available treatment modality for renal stones.
According to European Association of Urology (EAU) 2020 Guidelines, when active treatment of
renal stones of size <10 mm is indicated, primary treatment modality is either SWL or RIRS.
For stones of size > 20 mm, PNL is first line of treatment, however if it is contraindicated
then RIRS or SWL can be used. Stones of size 10-20 mm in non-lower pole calyx can be dealt
with SWL or Endourology (PNL or RIRS). Lower pole calyx stones of 10-20 mm with unfavorable
factors like steep infundibulo-pelvic angle, long calyx, long skin to stone distance, narrow
infundibulum and shock wave resistant stones need to be treated with endourology (PNL or
RIRS). However, favorable lower pole calyx stones of size 10-20 mm are recommended for SWL or
Endourology.5According to AUA guidelines6, in symptomatic patients with a total non-lower
pole renal stone burden ≤ 20 mm, SWL or RIRS can be offered. Patients with a total renal
stone burden > 20 mm, PNL are the first line therapy. For patients with < 10 mm lower pole
renal stones, SWL or RIRS is first line treatment. Patients shouldn't be offered SWL as first
line therapy to lower pole stones >10 mm. Patients with lower pole stones >10mm in size need
to be explained that PNL has a higher stone free rate but greater morbidity.
RIRS is occasionally associated with severe infectious complications.14 Reasons commonly
attributed to it are high intra-pelvic pressure, obstruction, infected urine and stone, break
in sterility of procedure etc. Ureteral Access Sheath (UAS) is one of the measure used to
decrease intra-pelvic pressure during stone fragmentation.13 Irrigation for RIRS is the
critical component for the success of procedure. For better vision during procedure,
irrigation pressure (IP) and irrigation flow (IF) needs to be increased. To avoid detrimental
effects of high pressure, intra-renal pressure (IRP) has to be lower than 22 mmHg (30 cm of
water (H2O))7. High pressure irrigation raises intrarenal pressure leading to pyelo-venous
and pyelo-lymphatic reflux which can lead to sepsis, septic shock, bleeding, infundibular
rupture.
Some studies have estimated that at an IP of ≤ 100 cm H2O (73 mmHg), IRPs remain lower than
30 cm H2O if Ureteric Access Sheath (UAS) bigger than 10/12 F is utilized. An IP of 200 cm
H2O (146 mmHg) may offer high irrigation flows but could result in IRPs > 40 cm H2O8,9.
During forced irrigation and stone fragmentation, IRP can rise upto 300mmHg for short
interval.15 Omar M. et al in another similar endourological procedure, PCNL which showed High
Irrigation Pressure (272 cm H2O) to be associated with a higher risk of SIRS (46%) compared
to low Irrigation Pressure (108.8 cm H2O) risk of 11%.10 Gravity irrigation at 100 cm of H2O
(73 mmHg), exerts IRP lower than 30 cm of H2O, however in pressure irrigation IRP increases
significantly higher. In this study Investigators want to compare between two groups in terms
of safety and efficacy.
Rationale and Justification of study Irrigation is required in RIRS for better vision and
smooth performance of surgery. However, high IP during RIRS is implicated for infective
complications. Comparative study of different pressures for irrigation during RIRS is
lacking. Investigators would like to study the safety and efficacy of gravity irrigation
versus pressure irrigation in RIRS.
Objectives
General objectives To study the safety and efficacy of gravity irrigation versus pressure
irrigation in RIRS Specific objectives
1. To study the demographic pattern of patients undergoing RIRS
2. To compare complications rate of gravity irrigation versus pressure irrigation in RIRS
3. To identify the stone clearance of gravity irrigation versus pressure irrigation in RIRS
4. To compare duration of stone fragmentation of gravity irrigation versus pressure
irrigation in RIRS
Research question Which irrigation system is safe and efficacious: gravity or pressure
irrigation? Research Hypothesis Null hypothesis There is no difference in terms of
safety (complications and length of hospital stay) and efficacy (stone free rate and
fragmentation time) between gravity and pressure irrigation in RIRS.
Alternative hypothesis There is difference in terms of safety and efficacy between
gravity and pressure irrigation in RIRS.
Research design and Methodology
Research method- Quantitative
Types of study- Prospective Randomized Controlled Trial
Study population- Patients undergoing RIRS surgery for renal calculi and who give
consent for study
Study site - Department of Urology and Renal Transplant Surgery
Sampling method -Random sampling
Sample size- Sample size calculation
N= 2 * { (Z 1-α + Z 1-β) / (d-δ)}2 *p* (1-p)
Basis for sample calculation is study by Omar M et al in another similar endo-urological
procedure, PCNL which showed High Irrigation Pressure (272 cm H2O) to be associated with
a higher risk of SIRS (46%) compared to low (108.8 cm H2O) Irrigation Pressure 11%).10
Expected time and duration of the study- 1 year
Tools and techniques for data collection
Data collection will be done using preformed proforma and entered in windows excel.
Patient's demographic profile, stone characteristics and pelvi-calyceal anatomy will be
recorded. Categorical variables will be expressed as proportions (%) and continuous
variables expressed as Mean ± Standard Deviation(SD). Chi-square test will be used for
categorical data and Mann-Whitney U test or student's t test will be applied for
continuous variables as appropriate.
Management protocol of patients
Patients with symptomatic renal calculi fulfilling inclusion criteria, will be
considered for RIRS. Pre-operative workup of patients includes Complete blood count,
Renal function test, Chest X ray, Electrocardiogram (ECG), Urine routine and microscopy,
Urine culture and sensitivity. Imaging work-up includes X-ray Kidney Ureter and Bladder
(KUB), Ultrasonography Abdomen and Pelvis and Computed Tomography (CT) Urography.
Pre-operatively R.I.R.S. scoring system is used to predict stone free rate.11 Patient
planned for surgery needs sterile urine. If patient has indwelling tube/catheter and
urine culture shows colonized organism, then patient will be treated with sensitive
antibiotics for at least 3 doses. Informed written consent will be taken from patient
and patient information sheet (PIS) will be given. Patient will be randomized to two
groups: gravity irrigation group and pressure irrigation group in 1:1 ratio through
computer generated random numbers. Even numbers will be assigned to gravity irrigation
group and odd numbers to pressure irrigation group. Patient will get prophylactic
antibiotic at the time of induction with single dose of ceftriaxone 1gm IV and amikacin
750 mg IV or sensitive antibiotics will be continued.
Patient will be placed in lithotomy position and rigid cystoscopy (19 Fr sheath and 30
scope) will done. Guidewire (Terumo 0.035 inch) will be parked into renal pelvis and
ureteric access sheath 9.5/11.5 Fr (Cook Medical, Bloomington) will be placed reaching
just proximal ureter under fluoroscopy. Flexible ureteroscopy will be done with Karl
Storz FLEX X2S connected to irrigation system consisting of intravenous infusion set
(JMS® Singapore PTE LTD, Singapore) connected to 1 Liter (L) normal saline compressible
plastic bottle (Aculife®, Aculife Healthcare Pvt. Ltd, Gujarat, India) placed at height
of 100 cm from patient's symphysis pubis. In Gravity irrigation group, RIRS surgery will
be done with 1 L normal saline bottle placed at 100 cm from patient's symphysis pubis.
In case of poor vision and procedure can't be completed with gravity irrigation,
pressure irrigation will be used and this conversion will be mentioned in proforma. In
pressure irrigation group, Irrigation pressure will be given by arterial line pressure
bag and will be started from 80 mmHg and subsequently increased by 10 mmHg as required
and peak irrigation pressure required will be noted.
Stones will be dusted and fragmented with laser energy (LithoDK30, Holmium 2.1
micrometer, Quanta System, Milan, Italy). Duration of surgery along with stone
fragmentation time will be noted. After the procedure, DJ stent will be placed and
removed after 2 weeks.
Stone clearance will be confirmed fluoroscopically at the completion of surgery, Post
operative day one (POD1) and Post operative month one (POM1) with X-ray KUB and USG
abdomen and pelvis. If patient requires more than one stage procedure, it will be
mentioned. Patient's post-operative course will be monitored and any complications will
be noted. For rapid identification of sepsis, quick Sequential Organ Failure Assessment
(qSOFA) score will be used: respiratory rate of 22/min or greater, altered mentation, or
systolic blood pressure of 100 mmHg or less. qSOFA score more than two alerts to
evaluate for sepsis and septic shock. Double J (DJ) stent will be placed for 2 weeks
unless its removal required because of fever. Post-operative complications will be
recorded as per classification described by Clavien-Dindo.12
Process of data Analysis Data collected in Proforma will be entered in Windows Excel.
Comparative analysis will be done between gravity irrigation versus pressure irrigation.
CONSORT Flow Diagram
Plan for data management and statistical analysis
Data collection will be done in proforma and will be entered in Windows Excel. Patient's
demographic profile, stone characteristics and pelvi-calyceal anatomy will be recorded.
Categorical variables will be expressed as proportions (%) and continuous variables
expressed as Mean ± SD. Chi-square test will be used for categorical data and
Mann-Whitney U test or student's t test will be applied for continuous variables as
appropriate. P value of <0.05 will be considered significant.
Biases and Limitations of the study
During procedure, vision is subjective and depends on surgeon's assessment and may
require high pressure to obtain optimum vision. Surgeon's patience is required to wait
till vision becomes clear. Size of stone, type and volume of stone, use of ureteric
access sheath, past history of DJ stent placement, past history of endourological
procedure as well as patient's comorbidities like diabetes mellitus, immunocompromised
status can be confounding factors for longer duration of surgery, complications and
stone clearance rate.
Safety considerations During evaluation and treatment of patient, safety and care of
patient will be taken. No unnecessary intervention or medication will be given to
patient apart from what is mentioned in our study and current best practice for
management of renal stones.
